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Biomedical subjects

F Birklein

Publications and source records attributed to F Birklein.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Vagus nerve stimulation - a new option for the treatment of chronic pain syndromes?].

Electrical stimulation of the vagal nerve (VNS) has become an established method for treating medically refractory epilepsies. From animal experiments it is well known that depending on the stimulation intensity VNS can elicit both inhibition and facilitation of nociception. Recent physiologic investigations demonstrated a similar influence of VNS on pain perception in patients treated by chronic VNS. However, in humans, a more marked effect was shown for the pain inhibition which is probably mediated by neurobiochemical mechanisms. These findings are discussed in consideration of the physiologic mechanisms underlying the modulation of pain and seizures by VNS known from animal studies. First reports of attenuation of chronic pain by VNS indicate that the method might be an option for pain treatment in the future.

Animals↗
PubMed2001

Facilitated neurogenic inflammation in complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is characterized by a variety of clinical features including spontaneous pain and hyperalgesia. Increased neuropeptide release from peripheral nociceptors has been suggested as a possible pathophysiologic mechanism triggering the combination of trophic changes, edema, vasodilatation and pain. In order to verify the increased neuropeptide release in CRPS, electrically induced neurogenic vasodilatation and protein extravasation were evaluated in patients and controls. We performed a prospective study on 10 patients with acute and untreated CRPS and 10 matched healthy controls. Neurogenic inflammation was elicited by strong transcutaneous electrical stimulation via intradermal microdialysis capillaries which simultaneously enabled measurement of protein extravasation. Laser-Doppler scanning was used to assess axon reflex vasodilatation. Axon reflex vasodilatation was significantly increased in CRPS patients (438 +/- 68% of baseline vs. 306 +/- 52%; P < 0.05) and transcutaneous electrical stimulation provoked protein extravasation only in the patients (before, 0.28 +/- 0.03 mg/ml; during stimulation, 0.34 +/- 0.04 mg/ml), whereas protein concentration steadily declined during stimulation in the healthy controls (before, 0.23 +/- 0.04 mg/ml; during stimulation, 0.18 +/- 0.04; P < 0.001). The time course of electrically induced protein extravasation in the patients resembled the one observed following application of exogenous substance P (SP). We conclude that neurogenic inflammation is facilitated in CRPS. Our results suggest an increased releasability of neuropeptides in CRPS.

Adult↗
PubMed2001

Despite clinical similarities there are significant differences between acute limb trauma and complex regional pain syndrome I (CRPS I).

In order to analyze the pathophysiology behind the clinical similarity acutely after limb trauma and in acute stages of complex regional pain syndrome (CRPS), 20 patients with external fixation after distal radius fracture (3.5 days after surgery) without signs of CRPS and 24 patients suffering from acute CRPS I (without nerve lesion; duration, 5 weeks) were investigated. Hyperalgesia to heat was tested by a feedback-controlled thermode, and to mechanical stimuli by an impact stimulator. The sympathetic nervous system was examined by measuring skin temperature (infra-red thermography), testing different sympathetic vasoconstrictor reflexes (laser-Doppler flowmetry) and quantitative sudometry after thermal load (thermoregulatory sweat test). We found hyperalgesia to heat after trauma (P<0.001), but not in CRPS, whereas mechanical hyperalgesia was present in both patient groups (trauma: P<0.001; CRPS: P<0.005). Skin temperature was significantly increased on the affected side in both patient groups (acute trauma: P<0.001; CRPS: P<0.005). However, sympathetic failure, as indicated by impairment of sympathetic vasoconstrictor reflexes (P<0.02) and hyperhidrosis (P<0.01), was found exclusively in CRPS patients. Our results indicate that pain and vasomotor disturbances may be generated by different mechanisms acutely after trauma and in acute CRPS. Despite the clinical similarity, additional changes in the peripheral or central nervous system are required for CRPS. In the light of our observations, it seems unlikely that CRPS is a simple exaggeration of post-traumatic inflammation.

Acute Disease↗
PubMed2001

Autonomic failure after stroke--is it indicative for pathophysiology of complex regional pain syndrome?

In order to find pieces of evidence for a central origin of autonomic failure in complex regional pain syndrome I (CRPS I), the pattern of autonomic symptoms in CRPS I patients was compared to patients a few days after stroke. Autonomic failure in the latter group is assumed to represent definite CNS origin. Seventeen stroke patients, 21 patients in the acute and late stage of CRPS I and a control group of 23 healthy subjects were investigated. Detailed neurological examination was performed, sweating was induced centrally (thermoregulatory sweating, TST) and peripherally by carbachol iontophoresis (QSART) and quantified by evaporation hygrometry. Skin temperature was assessed by infrared thermography. The incidence of motor-sensory dysfunction (without pain) and the incidence of edema was strikingly similar in stroke and CRPS patients. Furthermore, stroke patients had increased TST but not QSART responses on the contralesional limb (P < 0.05) and skin temperature was decreased (P < 0.001). The same pattern of autonomic failure was found in late CRPS (TST: P < 0.02, skin temperature: P < 0.01) whereas in acute CRPS additional, presumably peripheral mechanisms, contribute to sympathetic symptoms. In conclusion, our investigation suggests that many clinical symptoms and the main features of sympathetic dysfunction in CRPS could be explained by a CNS pathophysiology.

Adult↗
PubMed2001

Dose thresholds and duration of the local anhidrotic effect of botulinum toxin injections: measured by sudometry.

BACKGROUND: Local injections of botulinum toxin type A (BTX-A) have been used successfully to treat focal hyperhidrosis, but because experimental data were lacking, doses have been chosen arbitrarily or empirically. OBJECTIVES: To analyse dose dependency and duration of BTX-A-derived suppression of sweat gland activity. METHODS: Employing a standardized scheme (four injections, square 2 x 2 cm), different doses of BTX-A [Dysport(R); 2.5-120 mouse units (MU)] were injected subcutaneously at the lateral aspects of both of the lower legs in 15 healthy volunteers. Sweat tests were performed before, and 3 weeks and 6 months after, BTX-A injections. Sweating was visualized by staining with iodine starch, and quantified by capacitance hygrometry after carbachol iontophoresis, the quantitative sudomotor axon reflex test (QSART). RESULTS: Iodine starch staining indicated a threshold dose of 10 MU (2.5 MU cm-2) leading to visible anhidrotic skin spots after 3 weeks in all subjects. This was maintained for 6 months with doses of 50 MU (12.5 MU cm-2) or higher, but the size of the anhidrotic skin area decreased over time (P < 0.001) indicating partial recovery at the edges. After 3 weeks QSART was significantly reduced (P < 0.02) and completely suppressed by doses of 80 MU (20 MU cm-2) or more, although after 6 months QSART increased again to pre-BTX-A levels (P < 0.001). Both methods indicated that the suppression of sweating is dose dependent (QSART: r = -0.70, P < 0.001; iodine starch staining: r = 0.74, P < 0.001). CONCLUSIONS: Our findings suggest that BTX-A effectiveness can be quantified by testing sudomotor function. For the first time threshold doses for the suppression of sweating have been defined.

Adolescent↗
PubMed2000

Left vagus nerve stimulation suppresses experimentally induced pain.

OBJECTIVE: To test whether electric stimulation of the vagus nerve has an antinociceptive effect in humans. BACKGROUND: In a variety of animal studies, vagus nerve stimulation was shown to inhibit nociceptive behavior as well as electric responses of spinal nociceptive neurons. In humans, chronic left vagus nerve stimulation is used to treat pharmacologically refractory epilepsy. METHODS: The authors investigated experimental pain in 10 patients with seizures before and twice after implantation of a vagus nerve stimulator by using different controlled stimuli, including noxious heat, tonic pressure, and short impact. Pain was quantified on a visual analogue scale. Twelve nonepileptic age- and gender-matched individuals served as control subjects. RESULTS: Vagus nerve stimulation reduced increasing pain associated with trains of five consecutive stimuli at 1.5-second intervals ("wind-up"; p < 0.001). In a similar manner, pain on tonic pressure was reduced by vagus nerve stimulation (p < 0.03). Pain associated with single-impact stimuli as well as heat pain thresholds were unaltered under vagus nerve stimulation. Thus, vagus nerve stimulation led to pain relief predominantly in experimental procedures in which pain magnitude was amplified by central processing. The antinociceptive effect was independent of the acute on-off cycles of vagus nerve stimulation. CONCLUSIONS: Vagus nerve stimulation is effective in reducing pain in humans. In humans, the antinociceptive effect might rely on central inhibition rather than alterations of peripheral nociceptive mechanisms. These results indicate a promising, potential future role of vagus nerve stimulation in pain treatment.

Adult↗
PubMed2000

Increased skin lactate in complex regional pain syndrome: evidence for tissue hypoxia?

To investigate oxygen metabolism in complex regional pain syndrome (CRPS), the authors measured skin lactate via dermal microdialysis performed on patients with CRPS (n = 11) and healthy control subjects (n = 11). In addition, they measured blood lactate. Although venous lactate was unaltered, skin lactate was increased in patients with CRPS (2.95 mmol/L; control subjects 1.74 mmol/L; p < 0.005). These results suggest enhanced anaerobic glycolysis, probably as a result of chronic tissue hypoxia.

Adult↗
PubMed2000

Sudomotor testing discriminates between subjects with and without antibodies against botulinum toxin A--a preliminary observation.

With an increasing number of patients being treated with botulinum toxin A (BTX A), the incidence of neutralizing anti-BTX antibodies (ABA) is rising. Because BTX A is known to inhibit sweating, sudometry seems to be a promising tool to test the efficacy of BTX A. We injected BTX A subcutaneously in normal control subjects and four patients with spasmodic torticollis, two responders and two nonresponders with proven ABA. Sweating was visualized using iodine starch staining and quantified used capacitance hygrometry. BTX A inhibited sweating completely at the injection site in both control subjects and all responders without evidence for ABA. However, continued sweating was recorded when the nonresponders with proven ABA were tested. We conclude that sudomotor testing is able to discriminate between subjects with and without clinically important ABA.

Antibodies↗
PubMed2000

Experimental tissue acidosis leads to increased pain in complex regional pain syndrome (CRPS).

The aim of this study was to investigate the role of local acidosis in the generation of pain in complex regional pain syndrome (CRPS). We investigated ten patients with CRPS of the upper extremity with a mean duration of the disease of 43 weeks (range 4-280 weeks) and ten control subjects for sensitivity to infusion of fluids with low pH (pH 6.1). Another group of five CRPS patients and three healthy controls was investigated using the same protocol but neutral infusion fluid (pH 7.4). A motorized syringe pump was installed for a constant infusion of synthetic interstitial fluid (SIF, either acidified (pH 6.1) or neutral) into the skin at the back of the hands and, thereafter, into the interosseus I muscle on both sides. A flow rate of 30 ml/h was chosen for intradermal and 7.5 ml/h for intramuscular infusion over a period of 10 min. The magnitude of pain was rated on an electronic visual analogue scale. Patients were requested to give their ratings every 10 s during the whole stimulation period. The ratings were normalized as fractions of individual grand mean values. We found significantly increased pain perception during infusion of acidified SIF on the affected side in CRPS patients. Low pH fluid into the skin was significantly more painful between 4 and 6 min (ipsi 1.27 normalized rating (NR) (0. 19-1.94), contra 0.31 NR (0.03-0.51), P<0.02) and between 8 and 10 min (ipsi 1.38 NR (0.19-1.94), contra 0.08 NR (0-0.27), P<0.03) on the affected side, while analysis over the whole stimulation period just failed to reach statistical significance (ipsi 281 area under the curve (AUC) (187-834), contra 87 AUC (28-293), P=0.059). Low pH infusion into the muscle was significantly more painful on the affected side during the whole infusion time (ipsi 861 AUC (308-1377), contra 190 AUC (96-528), P<0.01). The quality of the deep pain during infusion into the muscle was described by the patients as very similar to the CRPS-related pain. In controls we found no side differences of pain intensity during low pH stimulation. Neutral SIF evoked no pain at all, neither in CRPS patients (ipsi 0 AUC, contra 0 AUC) nor in healthy controls. Our results suggest that hyperalgesia to protons is present in patients with CRPS. Further, we could demonstrate that pain is not only restricted to the skin but is also generated in deep somatic tissue of the affected limb.

Acidosis↗
PubMed2000

Neurological findings in complex regional pain syndromes--analysis of 145 cases.

Early diagnosis is a prerequisite for a successful treatment of complex regional pain syndrome (CRPS). In order to describe neurological symptoms which characterize CRPS, we evaluated 145 patients prospectively. Two-thirds of these were women, the mean age at time of investigation was 50.4 years. CRPS followed limb trauma, surgery and nerve lesion. Employing the current IASP criteria 122 patients were classified as CRPS I and 23 as CRPS II. All patients were assessed clinically pain was quantified using the McGill pain questionnaire, skin temperature was measured by an infrared thermometer and a subgroup of 57 patients was retested in order to determine thermal thresholds (QST). Of our patients 42% reported stressful life events in a close relationship to the onset of CRPS and 41% had a history of chronic pain before CRPS. The latter group of patients gave a higher rating of CRPS pain (P<0.05). The major symptoms were pain at rest in 77% and hyperalgesia in 94%. Typical pain was deep in the limb having a tearing character. Patients getting physical therapy had significantly less pain than those without (P<0.04). Autonomic signs were frequent (98%) and often changed with the duration of CRPS. Skin temperature was warmer in acute and colder in chronic stages (P<0.001). Likewise edema had a higher incidence in acute stages (P<0.001). We found no correlation between pain and autonomic dysfunction. Motor dysfunction (present in 97%) included weakness, tremor, exaggerated tendon reflexes, dystonia or myoclonic jerks. QST revealed increased warm perception thresholds (P<0.02) and decreased cold pain thresholds (P<0.03) of the affected limb. The detailed knowledge of clinical features of CRPS could help physicians early to recognize the disease and thus to improve therapy outcome.

Adolescent↗
PubMed1999

[Complex regional pain syndrome. Clinical and autonomic disorders during acute and chronic illness stages].

In order to describe autonomic dysfunction and clinical outcome in complex regional pain syndrome (CRPS) 20 patients were followed-up. First investigation was performed in the acute stage of CRPS and the second investigation two years later after therapy (individual, not standardized). Skin temperature and sudomotor function (thermoregulatory sweating (TST) and quantitative sudomotor axon reflex (QSART)) were assessed, and a clinical follow-up was performed carefully. Skin temperature was warmer on the affected side at first investigation (p < 0.001) and colder at follow-up (p < 0.02). Sudomotor output was enhanced on the affected side both after TST (p < 0.005) and QSART (p < 0.05) at first investigation. At follow-up, however, while thermoregulatory sweating was still increased (p < 0.04) QSART was not different. While autonomic failure improves as assessed by clinical examination, therapy failed to alleviate pain significantly. But patients' self-assesment of therapy was mostly positive (16 of 20, p < 0.001). The present study has shown that the autonomic failure may be probably the result of central disturbances of thermoregulation, but secondary peripheral mechanisms also contribute to our findings. Individual based therapy seems to be efficacious for long term treatment, but for final judge controlled studies are required.

Adult↗
PubMed1999

Patterns of hyperalgesia in complex regional pain syndrome.

Complex regional pain syndrome (CRPS) is characterized by a triad of sensory, motor and autonomic dysfunctions, with long-standing pain and temperature differences of the affected and contralateral limb as predominant symptoms. The pathogenesis of the disorder still remains unclear. Among the main hypotheses of an underlying pathophysiology we find inflammatory processes and dysfunction of the sympathetic nervous system. Whether the main site of dysfunction is found centrally or peripherally is not known. With psychophysical methods we studied patterns of hyperalgesia to obtain a better understanding of the neuropathic pain component in CRPS. Forty patients in an acute phase of CRPS and a median duration of the disease of 10 weeks, were included in the study. Hyperalgesia to heat was tested with a thermode providing feedback-controlled temperature increases. Two forms of mechanical hyperalgesia were examined: phasic mechanical stimuli by using a custom-made impact stimulator for the determination of individual pain thresholds, tonic mechanical stimuli were applied using a pinch-device. Additionally a 'wind-up' paradigm was used to study a pain phenomenon of presumed central origin: a defined impact stimulus was given once and five times in repetition. A subpopulation of patients was reevaluated for mechanical hyperalgesia after i.v. injection of 500 mg acetyl-salicylic acid. Hyperalgesia to heat was insignificant. We found, however, a marked mechanical hyperalgesia to phasic impact stimuli (P < 0.005), whereas, static stimulation (squeezing skin folds) results were insignificant again. Wind-up related pain was also significantly enhanced in the affected limb (P < 0.02). The anti-inflammatory agent had no effect. These results indicate a non-inflammatory pathogenesis in CRPS presumably central in origin.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

[The assessment of sudomotor function for diagnosis of autonomic diseases. Principles and methods].

Thermoregulatory and emotional sweating can be distinguished in humans. While the first is organized via feed back mechanisms involving thermoreceptors, thermoregulatory centers in the brain and the effector system (sympathetic nervous system and sweat glands), the latter is generated directly by cortical and limbic mechanisms without any feed back. Sweat glands on the hairy skin can be stimulated by thermoregulatory mechanisms (rising body temperature), the emotional sweating on the glabrous skin as a result of an arousal reaction and they can be stimulated by peripheral acting cholinergic agents, which initiate direct or axon reflex mediated sweating. To evaluate sweating there are qualitative methods that visualize the sweat response or indirect methods like the registration of skin potentials. Alternatively sweat output can be quantified by evaporative measurement. For best results these methods should be combined. In this way autonomic dysfunction e.g. after nerve lesions, in polyneuropathies, central lesions and certain pain disorders can be assessed. The sudomotor function tests complete the conventional electrophysiological methods.

Animals↗
PubMed1998

Spatial extension of sudomotor axon reflex sweating in human skin.

Acetylcholine (ACh) applied to human skin is known to elicit a sweat response, which consists of a direct muscarinergic (M3) activation of sweat glands and a nicotinic axon reflex response from sudomotor terminals. To visualize the extent of axon reflex sweating after ACh-iontophoresis, iodine starch staining was used. Iontophoresis was performed under occlusion at the peroneal aspects of the lower leg and the center of the foot dorsum of healthy volunteers (n = 10). Ten minutes after stimulation, the area of dark blue staining was recorded by a video camera. Control experiments were performed with saline, histamine, pilocarpine and nicotine iontophoresis. The stained area was measured and the maximum and minimum distance of its boundary from the edge of the iontophoresis probe was determined (maximum/minimum radius). Sizes of stained areas and maximum radii were significantly greater on the lower leg compared to the foot (P < 0.01). The median sizes of the stained areas on the leg were 14.6 cm2 and on the foot dorsum 8.0 cm2. The respective median maximum radii were 3.1 cm on the leg and 2.3 cm on the foot dorsum (median minimum, leg 1.1 cm, foot 0.8 cm). These results match microneurographic findings of innervation territories of sympathetic efferent units. Area sizes of stained skin showed a close correlation between both stimulation sites (R = 0.96, P < 0.01), i.e. the sizes of sweat responses on leg and foot show a constant relation (foot/leg = 0.57) in spite of their great interindividual variability. This novel technique of establishing sweat responses provides information on the size of sudomotor innervation territories and may be useful for clinical studies in patients with suspected impairment of sympathetic functions.

Acetylcholine↗
PubMed1998

Pattern of autonomic dysfunction in time course of complex regional pain syndrome.

The objective of the present investigation was to describe and localize autonomic dysfunction in acute and chronic stages of complex regional pain syndrome (CRPS). Patients were investigated twice: the first investigation was performed as soon as diagnosis was established during the acute stage of CRPS and the second investigation was performed about 2 years later. Twenty-one patients completed the follow-up investigation. The median duration of CRPS was 5 (range 2-21) weeks at first investigation and 94 weeks (22-148) at follow-up. Skin temperature was recorded by thermography, sudomotor function was assessed by thermoregulatory sweat test (TST) and quantitative sudomotor axon reflex test (QSART). Skin temperature was warmer on the affected side at the first investigation (P < 0.001) and colder at follow-up (P < 0.02) compared with the contralateral limb. Sudomotor output was enhanced after both TST (P < 0.005) and QSART (P < 0.05) at the first investigation on the affected side. However, at follow-up, sweating after TST was still increased (P < 0.04) while QSART responses were not different between the affected and unaffected limbs. As compared to controls there was no statistically significant difference, neither in skin temperature nor sweating, neither on the affected nor on the unaffected side. In conclusion, the present investigation proved that vasomotor and sudomotor control are substantially altered in CRPS. In the acute stage vasomotor control is decreased in the affected limb whereas sudomotor function is enhanced. This may be the result of disturbances of thermoregulation, but different secondary peripheral mechanisms, concerning vasomotor and sudomotor function, contribute to clinical presentation of CRPS and affect autonomic function at all stages of CRPS.

Adult↗
PubMed1997

Effects of cutaneous histamine application in patients with sympathetic reflex dystrophy.

Thirty-six patients suffering from acute reflex sympathetic dystrophy (RSD) were examined in order to evaluate nociceptive C-fibers. Axon reflex vasodilatation was induced by iontophoresis of histamine and recorded (laser Doppler flux). The strength of concomitant sensation was rated on a visual analogue scale, and the quality was characterized as itching or burning pain. Skin temperature was recorded by infrared thermography. The results were compared with investigations of unaffected limbs of patients and volunteers. The histamine-induced sensation on the symptomatic side was more often burning pain than itching (P < 0.001), and skin temperature was increased on the affected limb (P < 0.001). Axon reflex vasodilatation and the strength of sensations were unaltered. In conclusion, this study rules out a significant deterioration of afferent C-fibers in RSD, but gives evidence of sensitization of nociceptive function. This nociceptive sensitization has to be taken into consideration for effective treatment of RSD.

Adult↗
PubMed1997

Sudomotor function in sympathetic reflex dystrophy.

Sudomotor functions were studied in 27 patients suffering from reflex sympathetic dystrophy (RSD) according to the criteria established by Bonica (18 women, 9 men; mean age 50 +/- 12.3 years; median duration of disease 8 weeks, range 2-468 weeks). To measure local sweating rates, two small chambers (5 cm2) were affixed to corresponding areas of hairy skin on the affected and unaffected limbs. Dry nitrogen gas was passed through the chambers (270 ml/min) and evaporation was recorded at both devices with hygrometers. Thermoregulatory sweating (TST) was induced by raising body temperature (intake of 0.5 1 hot tea and infra-red irradiation). Local sweating was also induced through an axon reflex (QSART) by transcutaneous iontophoretic application of carbachol (5 min, 1 mA). In addition, skin temperature was measured on the affected and unaffected side by infra-red thermography. Mean skin temperature was significantly higher on the affected side (P < 0.003). In spite of the temperature differences, there was no difference in basal sweating on the affected and unaffected side. However, both methods of sudomotor stimulation lead to significantly greater sweating responses on the affected compared to the unaffected side (TST: P < 0.05, QSART: P < 0.004). Latency to onset of sweating was significantly shorter on the affected side under both test conditions (P < 0.04 and P < 0.003, respectively). Sweat responses were not correlated to absolute skin temperature but were probably related to the increased blood flow on the affected side. Our findings imply a differential disturbance of vasomotor and sudomotor mechanisms in affected skin. Whereas vasoconstrictor activity is apparently lowered, sudomotor output is either unaltered or may even be enhanced.

Axons↗